Pregnancy-associated plasma protein A

PAPPA
Identifiers
Aliases	PAPPA, ASBABP2, DIPLA1, IGFBP-4ase, PAPA, PAPP-A, PAPPA1, pappalysin 1
External IDs	OMIM: 176385 MGI: 97479 HomoloGene: 31097 GeneCards: PAPPA
Gene location (Human)
Chr.	Chromosome 9 (human)
End	116,402,321 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	65,275,746 bp
RNA expression pattern
	Top expressed in
	smooth muscle tissue; ; myometrium; ; organ system; ; myocardium; ; tendon;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	zinc ion binding; peptidase activity; endopeptidase activity; hydrolase activity; metallopeptidase activity; metal ion binding; metalloendopeptidase activity;
Cellular component	extracellular region; extracellular space;
Biological process	cellular protein metabolic process; proteolysis; response to follicle-stimulating hormone; female pregnancy; response to glucocorticoid;
	Sources:Amigo / QuickGO
Orthologs
	5069
	18491
	ENSG00000182752
	ENSMUSG00000028370
	Q13219
	Q8R4K8
	NM_002581
	NM_021362
	NP_002572
	NP_067337
	Wikidata
View/Edit Human	View/Edit Mouse

Pappalysin-1, also known as pregnancy-associated plasma protein A, is a protein encoded by the PAPPA gene in humans. PAPPA is a secreted protease whose main substrate is insulin-like growth factor binding proteins. Pappalysin-1 is also used in screening tests for Down syndrome.^[5]^[6]

Function[]

This gene encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). PAPPA's proteolytic function is activated upon collagen binding. It is thought to be involved in local proliferative processes such as wound healing and bone remodeling. Low plasma level of this protein has been suggested as a biochemical marker for pregnancies with aneuploid fetuses (fetuses with an abnormal number of chromosomes).^[6] For example, low PAPPA may be commonly seen in prenatal screening for Down syndrome.^[5] Low levels may alternatively predict issues with the placenta, resulting in adverse complications such as intrauterine growth restriction, preeclampsia, placental abruption, premature birth, or fetal death.

Interactions[]

Pregnancy-associated plasma protein A has been shown to interact with major basic protein.^[7]^[8]^[9]

Studies conducted at the Royal London Hospital in the United Kingdom, have shown that a marker of Down's syndrome may be expressed during the first trimester and second trimester of a pregnancy term. Concentrations of the Pregnancy-Associated Plasma Protein (PAPPA) gene as well as other markers can help screen for Down's syndrome in the beginning stages of a women's gestational period.^[10]^[11]

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000182752 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028370 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Breathnach FM, Malone FD (April 2007). "Screening for aneuploidy in first and second trimesters: is there an optimal paradigm?". Current Opinion in Obstetrics & Gynecology. 19 (2): 176–82. doi:10.1097/GCO.0b013e3280895e00. PMID 17353686. S2CID 25949255.
^ ^a ^b "Entrez Gene: PAPPA pregnancy-associated plasma protein A, pappalysin 1".
^ Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, et al. (October 2000). "Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor". The Journal of Biological Chemistry. 275 (40): 31128–33. doi:10.1074/jbc.M001384200. PMID 10913121.
^ Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C (January 2003). "Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment". The Journal of Biological Chemistry. 278 (4): 2106–17. doi:10.1074/jbc.M208777200. PMID 12421832.
^ Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L (June 1993). "Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein". The Journal of Biological Chemistry. 268 (17): 12243–6. doi:10.1016/S0021-9258(18)31378-4. PMID 7685339.
^ Alfirevic Z (February 2009). "Prenatal screening for Down's syndrome". BMJ. 338: b140. doi:10.1136/bmj.b140. PMID 19218324. S2CID 40516097.
^ Wald N, Stone R, Cuckle HS, Grudzinskas JG, Barkai G, Brambati B, et al. (July 1992). "First trimester concentrations of pregnancy associated plasma protein A and placental protein 14 in Down's syndrome". BMJ. 305 (6844): 28. doi:10.1136/bmj.305.6844.28. PMC 1882510. PMID 1379094.

Further reading[]

Sinosich MJ, Zakher A (1992). "Pregnancy-associated plasma protein A interaction with heparin: a critical appraisal". Gynecologic and Obstetric Investigation. 32 (2): 72–7. doi:10.1159/000292998. PMID 1721035.
Bischof P, Tseng L (April 1986). "In vitro release of pregnancy-associated plasma protein-A (PAPP-A) by human endometrial cells". American Journal of Reproductive Immunology and Microbiology. 10 (4): 139–42. doi:10.1111/j.1600-0897.1986.tb00013.x. PMID 2422961.
Bolton AE, Pinto-Furtado LG, Andrew CE, Chapman MG (June 1986). "Measurement of the pregnancy-associated proteins, placental protein 14 and pregnancy-associated plasma protein A in human seminal plasma". Clinical Reproduction and Fertility. 4 (3): 233–40. PMID 2427179.
Sinosich MJ, Saunders DM (January 1987). "Potential role of pregnancy-associated plasma protein-A in human reproduction". Journal of Reproductive Immunology. 10 (1): 55–65. doi:10.1016/0165-0378(87)90050-7. PMID 2438405.
Tornehave D, Chemnitz J, Teisner B, Folkersen J, Westergaard JG (1985). "Immunohistochemical demonstration of pregnancy-associated plasma protein A (PAPP-A) in the syncytiotrophoblast of the normal placenta at different gestational ages". Placenta. 5 (5): 427–31. doi:10.1016/S0143-4004(84)80023-5. PMID 6084247.
McIntyre JA, Hsi B, Faulk WP, Klopper A, Thomson R (November 1981). "Immunological studies of the human placenta: functional and morphological analysis of pregnancy-associated plasma protein A (PAPP-A)". Immunology. 44 (3): 577–83. PMC 1554973. PMID 6172371.
Bischof P, Geinoz A, Herrmann WL, Sizonenko PC (1984). "Pregnancy-associated plasma protein A (PAPP-A) specifically inhibits the third component of human complement (C3)". Placenta. 5 (1): 1–7. doi:10.1016/S0143-4004(84)80044-2. PMID 6203109.
Schindler AM, Bischof P (1984). "Histochemical localization of pregnancy-associated plasma protein A in fetal, infant, and adult organs and comparison between antisera". Gynecologic and Obstetric Investigation. 18 (2): 88–94. doi:10.1159/000299055. PMID 6207082.
Kristensen T, Oxvig C, Sand O, Møller NP, Sottrup-Jensen L (February 1994). "Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA". Biochemistry. 33 (6): 1592–8. doi:10.1021/bi00172a040. PMID 7508748.
Durham SK, Kiefer MC, Riggs BL, Conover CA (January 1994). "Regulation of insulin-like growth factor binding protein 4 by a specific insulin-like growth factor binding protein 4 proteinase in normal human osteoblast-like cells: implications in bone cell physiology". Journal of Bone and Mineral Research. 9 (1): 111–7. doi:10.1002/jbmr.5650090115. PMID 7512304. S2CID 42252996.
Bonno M, Oxvig C, Kephart GM, Wagner JM, Kristensen T, Sottrup-Jensen L, Gleich GJ (October 1994). "Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta". Laboratory Investigation; A Journal of Technical Methods and Pathology. 71 (4): 560–6. PMID 7526035.
Oxvig C, Haaning J, Kristensen L, Wagner JM, Rubin I, Stigbrand T, et al. (June 1995). "Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma". The Journal of Biological Chemistry. 270 (23): 13645–51. doi:10.1074/jbc.270.23.13645. PMID 7539791.
Zorin NA, Zhabin SG, Semenkov NN (July 1995). "Interaction of human pregnancy-associated plasma protein-A with serine proteinases". Clinica Chimica Acta; International Journal of Clinical Chemistry. 239 (1): 47–55. doi:10.1016/0009-8981(95)06098-X. PMID 7586586.
Silahtaroglu AN, Tümer Z, Kristensen T, Sottrup-Jensen L, Tommerup N (1993). "Assignment of the human gene for pregnancy-associated plasma protein A (PAPPA) to 9q33.1 by fluorescence in situ hybridization to mitotic and meiotic chromosomes". Cytogenetics and Cell Genetics. 62 (4): 214–6. doi:10.1159/000133479. PMID 7679961.
Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L (June 1993). "Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein". The Journal of Biological Chemistry. 268 (17): 12243–6. doi:10.1016/S0021-9258(18)31378-4. PMID 7685339.
Haaning J, Oxvig C, Overgaard MT, Ebbesen P, Kristensen T, Sottrup-Jensen L (April 1996). "Complete cDNA sequence of the preproform of human pregnancy-associated plasma protein-A. Evidence for expression in the brain and induction by cAMP". European Journal of Biochemistry. 237 (1): 159–63. doi:10.1111/j.1432-1033.1996.0159n.x. PMID 8620868.
Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, et al. (March 1999). "The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A". Proceedings of the National Academy of Sciences of the United States of America. 96 (6): 3149–53. Bibcode:1999PNAS...96.3149L. doi:10.1073/pnas.96.6.3149. PMC 15910. PMID 10077652.
Overgaard MT, Oxvig C, Christiansen M, Lawrence JB, Conover CA, Gleich GJ, et al. (October 1999). "Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues". Biology of Reproduction. 61 (4): 1083–9. doi:10.1095/biolreprod61.4.1083. PMID 10491647.
Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, et al. (October 2000). "Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor". The Journal of Biological Chemistry. 275 (40): 31128–33. doi:10.1074/jbc.M001384200. PMID 10913121.
Hourvitz A, Widger AE, Filho FL, Chang RJ, Adashi EY, Erickson GF (December 2000). "Pregnancy-associated plasma protein-A gene expression in human ovaries is restricted to healthy follicles and corpora lutea". The Journal of Clinical Endocrinology and Metabolism. 85 (12): 4916–20. doi:10.1210/jc.85.12.4916. PMID 11134163.

External links[]

The MEROPS online database for peptidases and their inhibitors: M43.004

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000182752 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028370 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[breathnach-5] Breathnach FM, Malone FD (April 2007). "Screening for aneuploidy in first and second trimesters: is there an optimal paradigm?". Current Opinion in Obstetrics & Gynecology. 19 (2): 176–82. doi:10.1097/GCO.0b013e3280895e00. PMID 17353686. S2CID 25949255.

[entrez-6] "Entrez Gene: PAPPA pregnancy-associated plasma protein A, pappalysin 1".

[pmid10913121-7] Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, et al. (October 2000). "Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor". The Journal of Biological Chemistry. 275 (40): 31128–33. doi:10.1074/jbc.M001384200. PMID 10913121.

[pmid12421832-8] Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C (January 2003). "Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment". The Journal of Biological Chemistry. 278 (4): 2106–17. doi:10.1074/jbc.M208777200. PMID 12421832.

[pmid7685339-9] Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L (June 1993). "Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein". The Journal of Biological Chemistry. 268 (17): 12243–6. doi:10.1016/S0021-9258(18)31378-4. PMID 7685339.

[pmid19218324-10] Alfirevic Z (February 2009). "Prenatal screening for Down's syndrome". BMJ. 338: b140. doi:10.1136/bmj.b140. PMID 19218324. S2CID 40516097.

[pmid1379094-11] Wald N, Stone R, Cuckle HS, Grudzinskas JG, Barkai G, Brambati B, et al. (July 1992). "First trimester concentrations of pregnancy associated plasma protein A and placental protein 14 in Down's syndrome". BMJ. 305 (6844): 28. doi:10.1136/bmj.305.6844.28. PMC 1882510. PMID 1379094.

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v t Proteases: metalloendopeptidases (EC 3.4.24)
ADAM proteins	Alpha secretases ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
Matrix metalloproteinases	Collagenases MMP1 MMP8 Gelatinases MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
Other	Neprilysin Procollagen peptidase Thermolysin Pregnancy-associated plasma protein A Bone morphogenetic protein 1 Lysostaphin Insulin-degrading enzyme ZMPSTE24